Ewing family of tumors
Ewing sarcoma/peripheral primitive neuro-ectodermal tumor (PNET) is a round-cell sarcoma that may show varying degrees of neuro-ectodermal differentiation.
These tumors are identified by a characteristic round-cell morphology and immunohistochemical profile, as well as by specific translocations involving the EWS gene on chromosome 22 and the 3’ portion of the E26 transformation-specific family of transcription factors.
These translocations result in fusion proteins that act as aberrant transcription factors. The majority of Ewing sarcoma cases are characterized by a balanced t(11;22).
Specific chromosomal abnormalities often correlate with distinct morphologic or phenotypic subtypes of tumors and play an important role in prognosis.
As neuroblastic tumors (neuroblastoma), Ewing sarcoma and primitive neuroectodermal tumors (PNETs) are closely related neoplasms supposedly derived from the neural crest.
Types
Ewing sarcoma
pPNET (peripheral primitive neuroectodermal tumors)
- Ewing family of tumors with epithelial differentiation (#18769338#)
Variants
"adamantinoma-like" variant
spindled variant
sclerosing variant
clear cell variant
anaplastic variant
neuroendocrine variant
Localization
bones
extra-osseous ES/PNET tumors
- soft tissue
- kidneys
- vulva and vagina (#17557870#)
Cytogenetics and molecular biology
22q12 reaarangements (EWS or EWSR1)
- t(11;22)(q24;q12) (EWSR1/FLI1 fusion gene) (90-95%)
- t(21;22)(q22;q12) (EWSR1/ERG fusion gene) (5-10%)
- t(2;22)(q33;q12) (EWSR1/FEV fusion gene)
- t(2;11;22)(q33;q24;q12)
- t(7;22)(p22;q12) (EWSR1/ETV1 fusion gene)
- t(17;22)(q21;q12) (EWSR1/ETV4 fusion gene)
other 22q12 rearrangements
- der(22)r(20;22) with amplification of the proximal region of the EWSR1 gene (#17175374#)
t(16;21)(p11;q22) (FUS/ERG fusion gene) (#1290763#)
variant translocations involving a third chromosome: 4q21, 5q31, 6p21, 7q12, 10p11.2, 12q14, 14q11, 18p23
chromosomal insertions
- 22q12 insertion in Chr.21 or Chr.11
- 21q21-q22 insertion in 22q12 (#15899394#)
secondary chromosomal changes (50%)
- 8+
- 12+
- unbalanced tranlocations involving Chr.1 or Chr.16
- 1p- 1p deletion
References
A novel t(4;22)(q31;q12) produces an EWSR1-SMARCA5 fusion in extraskeletal Ewing sarcoma/primitive neuroectodermal tumor. Sumegi J, Nishio J, Nelson M, Frayer RW, Perry D, Bridge JA. Mod Pathol. 2011 Mar;24(3):333-42. PMID: #21113140# [Free]
Aurias A, Rimbaut C, Buffe D, Zucker JM, Mazabraud A. Translocation involving chromosome 22 in Ewing’s sarcoma. A cytogenetic study of four fresh tumors. Cancer Genet Cytogenet. 1984 May;12(1):21-5. PMID: #6713357#
Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM. Chromosome study of Ewing’s sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12). Cancer Genet Cytogenet. 1984 May;12(1):1-19. PMID: #6713356#
Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir G. [Chromosomal translocation (11; 22) in cell lines of Ewing’s sarcoma] C R Seances Acad Sci III. 1983;296(23):1101-3. PMID: #6416622#